Caspase 9-induced apoptosis enables efficient fetal cell ablation and disease modeling.

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Tác giả: Toshinari Fujimoto, Shohei Fukunaga, Takumi Ikeda, Yuka Inage, Shiho Kawagoe, Yoshitaka Kinoshita, Eiji Kobayashi, Nagisa Koda, Takafumi Kuroda, Kenji Matsui, Kei Matsumoto, Keita Morimoto, Hinari Ohashi, Yatsumu Saito, Susumu Tajiri, Masahito Watanabe, Shutaro Yamamoto, Shuichiro Yamanaka, Takashi Yokoo

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Nature communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 714384

Fetal cell ablation models are crucial for studying congenital diseases, organ regeneration, and xenotransplantation. However, conventional knockout models offer limited control over disease severity, while conditional ablation models often require fetus-harming inducers. In the present study, we demonstrate that the inducible caspase 9 system enables precise targeting of fetal nephron progenitor cells in mice through the intrinsic apoptotic pathway. Using a safe, placenta-permeable inducer, this system facilitates specific, rapid, and efficient cell ablation. The system's temporal control allows precise adjustment of disease severity, generating reproducible models ranging from congenital kidney deficiency to severe chronic kidney disease. Cells with low expression levels of inducible caspase 9 and those in solid organs are less susceptible to apoptosis. However, this limitation can be overcome by inhibiting the X-linked inhibitor of apoptosis protein, thereby expanding the system's applicability. Additionally, this model provides a developmental environment suitable for chimeric kidney regeneration. This system advances understanding of induced cell death mechanisms, enhances pathological research tools, and supports therapeutic development in kidney disease and xenotransplantation applications.
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